Sci Trans Med: The "partner" of anti-tumor immunotherapy has been found!

!---- In recent years, the rapid development of tumor immunotherapy has led to a major breakthrough in the field of tumor therapy, the use of immunocheckpoint inhibitors to release anti-tumor immune responses has revolutionized cancer treatment, but only a few tumor types currently benefit from immunocheckpoint therapy (ICT), and a significant proportion of patients are unresponsive or resistant to ICT, scientists call immunotherapy-in-response tumors "cold" tumors, if you can understand the tumor's internal response or escape mechanism, it may be possible to make the tumor "hot" (hot tumor)On July 8,, researchers from the Cancer Center of the Sanford Burnham Prebys Institute for Medical Discovery in the United States and the Technical Comprehensive Cancer Center at the Haifa Institute of Technology in Israel found a way to turn "cold tumors" into "hot tumors."they published an article in the journal Science Translational Medicine on the immune escape mechanism of tumors, confirming the therapeutic potential of epigenetic modifiers PRMT5 inhibitors to make non-reactive melanoma sensitive to immunocheckpoint therapyDOI: 10.1126/scitranslmed.aaz5683 epigenetic modifier PRMT5 (protein arginine methyl metastase 5) controls a variety of cellular processes and participates in the development and process of cancerresearchers found that PRMT5 hides tumors from the immune system by controlling two immune signalsinhibition of PRMT5 enhances the activation of antigen presentation and innate immunity (which is a prerequisite for effective immunocheckpoint treatment)researchers are optimistic that the study will be a boon for those who are not responding to cancer immunotherapyregulatory antigenpresentation presented in the study, the researchers used a mouse melanoma model to show that the combination of PRMT5 inhibitors with anti-PD-1 therapy, one of the most commonly used immunocheckpoint therapy, succeeded in "heating up" non-reactive "cold" tumorsmice that normally do not respond to PD-1 treatments survive longer after receiving PRMT5 inhibitors and have smaller tumorsthis is due to the increased ability of the immune system to attack tumorsspecifically, the reduction in the expression of PRMT5 in melanoma cells increased the expression of the NLRC5 target gene involved in antigen processing and delivery, in contrast, the high expression of PRMT5 in cells reduces NLRC5 and inhibits the expression of its target genesin addition, the genetic inhibition of PRMT5 increases the abundance of cytokines involved in antigen processing and presentationthese findings show that PRMT5 restricts antigen processing and presentation by regulating NLRC5 transcriptionPRMT5 regulated the production of antigens by controlling NLRC5 expression inhibited cytokines, and researchers found that decreased activity of PRMT5 in melanoma cells increased the expression of Ifnb1 and 2 chemofactors Ccl5 and Cxcl10, instead, PRMT5 overexpression reduced the expression of more than three genes in cellsthese results show that PRMT5 inhibits the production of interferon-beta and chemofactors, the researchers also found that PRMT5 can affect the conduction of cGAS-STING signalsinhibition of PRMT5 in melanoma cells increases the phosphisms and dipolymerization of STING, PRMT5 inhibits the activation of the cGAS/STING pathway in melanoma cells and inhibits the production of interferons and chemofactorsPRMT5 regulatory cGAS/STING pathway inhibits cytokines In this study, the researchers identified two cell signaling pathways suppressed by PRMT5, allowing tumors to escape immune system detectionone way to be responsible for antigen presentation, and the second way to control the production of cytokines and innate immunitythese pathways together determine the extent to which tumors are able to escape from the immune system, their inhibition sedifys tumors that the immune system cannot seebased on these findings, it may be possible to help immunocheckpoint patients with tumors other than melanoma who fail to treat them